The goal of this research effort is to demonstrate that significant biomedical polymers can selectively affect the activation, function and Interleukin 1 (IL1) and other Growth Factor production of tissue macrophages and this modulation of macrophage activity can be correlated to in vitro and in vivo cellular proliferation and synthesis. The macrophage is considered to be the major cellular component controlling the inflammatory response and the biocompatibility of the implanted biomedical polymer. Macrophage activation is known to lead to IL1, PDGF, bFGF, TGF-beta and TNF-alpha production, all of which affect fibroblast, smooth muscle cell and endothelial cell proliferation and synthesis. Studies described in this application are directed toward understanding the biocompatibility of biomedical polymers and tissue/material interactions which lead to cellular proliferation and synthesis. Specifically, we will (1) evaluate the in vitro and in vivo effect of significant biomedical polymers, without and with preadsorbed proteins, on the activation and IL1 and other growth factor production of human and rat macrophages, and (2) evaluate the effect of in vitro and in vivo polymer-induced production of these macrophage mediators on the human fibroblast proliferation and synthesis (collagen), endothelial cell proliferation and synthesis (6-keto-PGF1 alpha, PA) and smooth muscle cell proliferation. Correlative data relating the in vitro and in vivo behavior of macrophages will be provided using cell culture bioassays. Results from the cell culture bioassays will be compared to results from in vivo subcutaneous implant studies to provide further in vitro-in vivo correlations. Significant biomedical polymers to be studied include polyethylene (NHLBI-DTB), PDMS (NHLBI-DTB), Silicone Rubber, woven Dacron, ePTFE, Biomer, Pellethanes, Polyurethaneurea Reference Materials (NHLBI-DTB) and Polyurethaneureas. The proteins which will be pre-adsorbed onto the polymers prior to evaluation are albumin, fibrinogen, fibronectin, immunoglobulin G, and complement component C5a. The important studies provide a quantitative understanding of biomedical polymer biocompatibility from a cell interaction and activation perspective. Results from the in vitro and in vivo studies proposed in this application will provide insight into cell- material, cell-protein and cell-cell interactions as they relate to the biocompatibility of polymers.